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Glucose metabolism after bariatric surgery: implications for T2DM remission and hypoglycaemia

Abstract

Although promising therapeutics are in the pipeline, bariatric surgery (also known as metabolic surgery) remains our most effective strategy for the treatment of obesity and type 2 diabetes mellitus (T2DM). Of the many available options, Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) are currently the most widely used procedures. RYGB and VSG have very different anatomical restructuring but both surgeries are effective, to varying degrees, at inducing weight loss and T2DM remission. Both weight loss-dependent and weight loss-independent alterations in multiple tissues (such as the intestine, liver, pancreas, adipose tissue and skeletal muscle) yield net improvements in insulin resistance, insulin secretion and insulin-independent glucose metabolism. In a subset of patients, post-bariatric hypoglycaemia can develop months to years after surgery, potentially reflecting the extreme effects of potent glucose reduction after surgery. This Review addresses the effects of bariatric surgery on glucose regulation and the potential mechanisms responsible for both the resolution of T2DM and the induction of hypoglycaemia.

Key points

  • Roux-en-Y gastric bypass and vertical sleeve gastrectomy are the two most widely used forms of bariatric surgery; both induce considerable weight loss and can induce remission of type 2 diabetes mellitus (T2DM) in some patients.

  • Bariatric surgery has important weight loss-dependent and weight loss-independent mechanisms for the induction of resolution of T2DM.

  • Bariatric surgery affects the glucoregulatory function of multiple target organs, including the intestine, liver, pancreas, adipose tissue and skeletal muscle.

  • In a subset of patients, post-bariatric hypoglycaemia can develop months to years after surgery, thereby representing a potential extreme example of altered glucose metabolism.

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Fig. 1: Weight loss-dependent and weight loss-independent mechanisms of bariatric surgery on glucose metabolism.
Fig. 2: Bariatric surgery-induced changes in bile acid dynamics induce alterations in glucose metabolism.
Fig. 3: Target organ responses to RYGB and VSG.
Fig. 4: An example of a daily pattern of glucose in a patient with post-bariatric hypoglycaemia.
Fig. 5: Timeline of physiological changes occurring after bariatric surgery.
Fig. 6: Changes in glucose regulation after bariatric surgery that hwave been linked to post-bariatric hypoglycaemia.

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M.E.P. reports personal consulting fees from Astra Zeneca, Fractyl, Hanmi Pharmaceutical, MBX Biosciences, Recordati, Poxel, Eiger Pharmaceuticals, and Xeris and grants from Chan-Zuckerberg Initiative, Dexcom and Helmsley Trust, outside the submitted work. D.A.S. reports consulting fees from Metis Therapeutics, outside the submitted work.

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Sandoval, D.A., Patti, M.E. Glucose metabolism after bariatric surgery: implications for T2DM remission and hypoglycaemia. Nat Rev Endocrinol (2022). https://doi.org/10.1038/s41574-022-00757-5

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